The present invention relates to a method for the preparation of starch particles by means of which small starch particles having a particle size of 50 nm to a few mm can be obtained in a simple manner. In particular small starch particles having a particle size of 50 nm to 100 xcexcm, so-called nano- or micro-particles, are highly desirable for a broad range of applications. Small starch particles can be used in pharmacy, cosmetics, foods, paints, coatings, paper, inks and many other applications.
Up to now small particles of this type have been prepared using polymers as starting materials by means of (multiple) emulsion cross-linking or solvent evaporation, spray-drying and other methods (Jiugao, Y. et al., Starch 46 (1994) 252; Arshady, R., Pol. Eng. Sci., 29 (1989), 1747). A number of routes are described in the following patents: PCT/GB/01735, PCT/GB95/00686, PCT/GB92/01692, PCT/GB93/01421, EP 0 213 303 B1. In EP 0 213 303 B1 two immiscible aqueous liquid phases are used as the starting material. In the case of emulsion cross-linking a great deal of mechanical energy is required and it is very difficult to separate off and to purify the particles, which leads to high production costs (for example in PCT/GB93/01692). Evaporation and spray-drying are also expensive techniques which demand the use of large quantities of (usually organic, volatile) solvents. A polymer or starch dissolved in water is always used as the starting material. In PCT/GB95/00686 a combination of a water-soluble and water-insoluble polymer is used as the starting material. However, both are dissolved in two different solvents.
The present invention now provides a method for the preparation of starch particles using a two-phase system with starch as a third main component. The method comprises at least the following steps:
a) preparation of a first phase comprising a dispersion of starch in water;
b) preparation of a dispersion or emulsion of the first phase in a second liquid phase, with the proviso that the second phase is not water;
c) cross-linking of the starch present in the first phase;
d) separating the starch particles thus formed.
According to the present invention starch is understood to be native starch, granular starch, fractions and derivatives of starch and agricultural raw materials which are rich in starch, (containing at least 80% starch wt./wt.), such as wheat flour. The starch can originate from a wide variety of natural sources, such as wheat, corn, amylocorn, wax corn, potatoes, quinoa, rice, etc.
Preferably, the starch is granular starch which can be native or modified, for example physically, chemically or enzymatically modified. The starch does not have to be soluble in water cold. Optionally the starch can also be fully or partially gelatinised or melted. A mixture of various types of starch can also be used. For instance, partially soluble, (pre-)gelatinised or modified starch can be added to native starch.
Partially or completely fractionated starch, such as starch enriched in amylose or, on the contrary, enriched in amylopectin, can also be used. Derivatives which can be used are partially or completely hydrolysed starch, such as maltodextrins, in which context hydrolysis can be under the influence of heat or acid, basic or enzymatic hydrolysis, oxidised starch (carboxy, dialdehyde, etc.), carboxylated, chlorinated or sulphated starch, starch that has been rendered hydrophobic (esters, such as acetate, succinate, half-esters, phosphate esters) and phosphated starch, starch ethers (hydroxyalkyl), and the like. Furthermore, starches with combinations of the abovementioned modifications, i.e. bifunctional or multifunctional starch, can also be used. The derivatives can also be granular.
Other carbohydrates or polymers can be used as auxiliaries. These auxiliaries make up at most 15%, preferably 1-10% (wt./wt. based on starch solids). Said auxiliaries include, in particular, other carbohydrates such as alginates, pectins and carboxymethylcellulose.
According to a first aspect of the present invention, the second phase is a hydrophobic phase. Said second phase is dispersed or emulsified in the first phase (starch-in-water) in such a way that an oil-in-water (O/W) emulsion is produced (step b) i)). Said O/W emulsion is then inverted to a water-in-oil (W/O) emulsion (step b) ii)). This process is referred to as xe2x80x9cphase inversionxe2x80x9d in this application. In the W/O emulsion the aqueous phase consists of the first water-in-starch phase. The starch can be granular, partially gelatinised or dissolved here. Following the phase inversion step, the starch particles are cross-linked and then separated.
The cross-linking reaction can already have been started before or during phase inversion. This method can be used in particular if the conditions for the cross-linking reaction are such that the cross-linking reaction proceeds slowly. Complete cross-linking in general takes place after phase inversion.
The starch does not yet have to be completely gelatinised at the start of the method. According to a preferred embodiment of the invention, partial or complete further gelatinising of the granular starch is effected during, before or after phase inversion. The starch can remain partially granular during cross-linking. Gelatinising can be effected by means of raising the temperature or by adding salts, such as hydroxides, or by a combination thereof.
It is advantageous if in step b) the ratio of hydrophobic phase:water in the O/W emulsion is of the order of magnitude of 80:20 to 20:80. Preferably, the ratio of hydrophobic phase:water in the O/W emulsion is between 60:40 and 40:60 (V/V).
All liquids which are not miscible with water are suitable as hydrophobic phase. Examples of these are hydrocarbons (alkanes, cycloalkanes), ethers, esters, halogeno-hydrocarbons, di- and triglycerides, fats, waxes and oils. Examples of oils or fats are palm oil, kernel oil, sunflower oil and salad oil. A number of apolar liquids are octane, dodecane, toluene, decalin, xylene, higher alcohols such as pentanol and octanol, or a mixture thereof. Paraffin oil, hexane or cyclohexane are preferably used. Preferably the viscosity of the hydrophobic phase is close to the viscosity of the starch/water phase. The miscibility of the water/starch phase with the hydrophobic phase preferably has to be as low as possible.
Preferably the O/W emulsion is stabilised with the aid of a surfactant. Phase inversion, i.e. the inversion from O/W emulsion to a W/O emulsion (step b) ii)), can take place in various ways. 1) If a surfactant is used which is temperature-sensitive, the phase inversion can be induced by raising the temperature. 2) The O/W emulsion can be destabilised by adding another surfactant. This surfactant stabilises a W/O emulsion. 3)
Phase inversion can be obtained by adding a hydrophobic liquid. 4) Phase inversion can also be obtained with the aid of the addition of salts.
Phase inversion by means of raising the temperature may be mentioned first. Raising the temperature gives rise to a shift of the surfactant molecules at the O/W interface towards the oil phase. The result of this is that the protection which the polar head provides against coalescence of the hydrophobic phase also decreases. At a certain temperature, which is dependent on, for example, the hydrophobic phase, type of surfactant and type and concentration of starch in the aqueous phase, the protection has decreased to such an extent that all oil droplets coalesce and the emulsion changes over or inverts from O/W to W/O.
The phase inversion temperature (PIT) is dependent on the chosen (water/starch)/oil (hydrophobic phase)/surfactant system. The surfactant concerned must preferably have an equal affinity for water and the hydrophobic phase, for example an oil. This is expressed in the HLB (hydrophilic-lipophilic balance) value. Preferably surfactants are used which have a HLB value of 8 to 20 or more preferentially of 10 to 15. The higher the HLB value the greater is the affinity of the surfactant for the aqueous phase. If this value becomes too high a much greater rise in temperature (or the addition of surfactant or hydrophobic liquid or salt) is needed in order to make phase inversion possible, or there is even no longer any phase inversion at all.
In principle, a wide variety of surfactants or emulsifiers can be used, such as fatty acid monoglycerides, such as Dimodan, Acidan (distilled monoglyceride) and glycerol monostearate, citric, lactic and acetic acid esters of fatty acids (Cetodan, Lactodan, Panodan, Promodan), propylene glycol esters of fatty acids (Triodan), sorbitan monolaurate, sorbitan monopalmitate, calcium stearate, ethoxylated and succinylated monoglycerides, glucose and sucrose esters; also fatty acid alcohols (cetanol, palmitol, stearyl alcohol), free fatty acids, lipids, phospholipids, lecithins, glycolipids and glycols. Examples of very suitable surfactants are those having a polar polyoxyethylene head. Such surfactants are, in particular, marketed under the trade name Tween. Tween-85 (polyoxyethylene (20) sorbitan trioleate, HLB=11xc2x11) is preferably used.
As stated above: the temperature at which phase inversion takes place is dependent on various factors, such as the type and to a lesser extent the concentration of the surfactant. The PIT can, for example, be lowered by:
increasing the salt concentration in the emulsion;
reducing the water:oil ratio;
adding an alcohol;
raising or lowering the pH, depending on the type of surfactant.
Preferably the water/oil (hydrophobic phase)/surfactant system is so chosen that a temperature rise of only 20xc2x0 C., preferably only 10xc2x0 C., is sufficient to effect phase inversion. Preferably phase inversion takes place at between 0 and 80xc2x0 C., more preferably at somewhat above room temperature (approx. 25-40xc2x0 C.).
A second method for allowing phase inversion to take place is the addition of a second surfactant. Said second surfactant differs from the surfactant used to stabilise the O/W emulsion. If the O/W emulsion has been stabilised with Tween 80, Span 80 can be added, for example.
Furthermore, the changeover from O/W emulsion to W/O emulsion is obtained by adding a hydrophobic liquid or a salt to the O/W emulsion. The change or inversion takes place by changing the volume fractions of the water and oil phases or, respectively, changing the surface tension at the interface. In fact, the addition of a hydrophobic liquid or salt to the O/W emulsion can also be regarded as lowering the phase inversion temperature.
One advantage of the use of this method (phase inversion) is that the formation of the W/O emulsion is a spontaneous process, so that little mechanical energy is needed for emulsifying the system. This also offers advantages when the system is scaled up. Especially when the PIT method is used, separating off the particles is simple in many cases. This can be effected by means of lowering the temperature, as a result of which the W/O emulsion is destabilised. Separation can also be achieved by adding apolar solvents, preferably an apolar alcohol, more preferably cyclohexanol or cyclooctanol.
Another advantage of this system is that the particle size can be adjusted to that desired by adjusting the process conditions, such as by suitable choice of the components of the system.
Following phase inversion the starch that has been dispersed or, optionally partially, dissolved in the aqueous phase is cross-linked. The cross-linking reaction can be started before, during or after phase inversion. As a result of this reaction discrete starch particles are produced. These particles can then be separated off.
Cross-linking can be effected by means of a cross-linking agent which preferably is added to the starch/water phase. This can take place before phase inversion or during or just after phase inversion, which mainly is determined by the rate of reaction. Depending on the cross-linking agent, cross-linking can be initiated by adding a catalyst, such as a base, acid or salt.
Cross-linking preferably takes place at between 0 and 80xc2x0 C., preferably between 10 and 60xc2x0 C. It is obvious that cross-linking takes place at a temperature which is above the phase inversion temperature, preferably at least 10xc2x0 C. and more preferentially at least 20xc2x0 C. above the phase inversion temperature.
Preferably 5 to 1000 mmol, more preferably 20-500 mmol, cross-linking agent is used per mol anhydroglucose unit.
Cross-linking agents which can be used are the most common bifunctional or multifunctional reagents. Examples of cross-linking agents are the common cross-linking agents such as epichlorohydrin, glyoxal, trisodium trimetaphosphate, phosphoryl chloride or an anhydride of a dibasic or polybasic carboxylic acid. However, the use of a phosphate, such as trisodium trimetaphosphate, as cross-linking agent is particularly preferred. In these cases the catalyst can be a base such as sodium hydroxide.
A variety of other cross-linking agents are possible when modified starches are used. In the case of dialdehyde-starch the cross-linking agent can be, for example, a diamine or diamide, such as urea, tetramethylenediamine or hexamethylenediamine, in which case an acid can be used as catalyst.
Cross-linking can also be carried out using a diamine or a diol in the case of, for example, carboxymethylstarch or dicarboxystarch. However, here cross-linking can also, and advantageously, be achieved by internal ester formation, which can be catalysed by a multivalent metal ion such as calcium, magnesium, aluminium, zinc or iron, preferably calcium. Another possible starting material is cationic or aminoalkyl starch, which can be cross-linked in situ using a dicarboxylic acid or a dialdehyde.
A few other cross-linking agents are: functional epoxides such as diepoxybutane, diglycidyl ether and alkylene bis-glycidyl ethers, dichlorohydrin, dibromohydrin, adipic anhydride, glutaraldehyde, amino acids and borax.
In a number of cases it is also possible to allow a chemical modification of the starch, for example a carboxymethylation or cationisation reaction, to take place simultaneously during the cross-linking reaction.
According to a second aspect of the present invention the second phase consists of a non-solvent for starch that is readily (or completely) miscible with water over a broad concentration range. At a certain ratio between the non-solvent and water the system is no longer completely miscible and phase separation occurs, small droplets of a starch aqueous phase being present in a continuous non-solvent phase.
According to this embodiment the present invention comprises a method for the preparation of starch particles in a two-phase system, wherein the second phase is a water-miscible non-solvent for starch, which method comprises:
a) preparation of a first phase comprising a dispersion of starch in water;
b) addition of the second phase to the first phase such that phase separation occurs;
c) cross-linking of the starch present in the first phase; and
d) separating the starch particles thus formed.
Any liquid which is miscible with water and in which starch does not dissolve can be used as non-solvent for starch. Examples of such non-solvents are acetone, methanol, ethanol and isopropanol.
Ethanol is preferably used. The quantity of ethanol, during reaction, is preferably between 20 and 75%, more preferably between 45 and 55%, with respect to the quantity of the first starch-in-water phase. The condition is that a phase-separated system is obtained. The quantity is dependent on the other components, such as the starch.
Preferably, the preparation is carried out at 0-80xc2x0 C., more preferably 10-60xc2x0 C.
The method of cross-linking with this method corresponds to that which has been described above. Preferably 5 to 1000 mmol, more preferably 20-500 mmol, cross-linking agent is used per mol anhydroglucose unit.
With this method as well the starch does not yet have to be completely gelatinised at the start of the method. According to a preferred embodiment of the invention, partial or complete further gelatinising of the granular starch is effected during, before or after the addition of the non-solvent to the first phase. The starch can remain partially granular during cross-linking.
The particle size of these particles is between 50 nm and 100 xcexcm. The particle size is dependent on, inter alia, starch and cross-linking agent type and concentration, reaction time and the type of non-solvent. This method as well offers the advantage that the particle size can be adjusted by adjusting the process conditions, including the various components.
Following cross-linking the particles can be separated off in a very simple manner by means of centrifuging or filtering off and drying. If necessary a little additional non-solvent is added to destabilise the system. The particles can be used immediately in applications in suspension, after partial drying. The particles can be dried in air, optionally after washing with water, ethanol or acetone, etc., or using existing drying techniques, such as roller drying, freeze drying or spray drying.
Another advantage of this method for the preparation of particles is that no surfactants are required and no acid or salt is needed to be able to separate off the particles. Consequently, re-use of the non-solvent is also possible in a simple manner.
The starch particles can be used, inter alia, in paper, textiles, explosives, foams, adhesives, hot melts, detergents, hydrogels, fertilisers, foods, artificial odours and flavourings, pharmaceutical and cosmetic products, tissues, soil improvers, pesticides, coatings, coatings removable by a mild treatment, for instance by means of enzymes or hot water, paints, inks, toners, organic reactions, catalysis, ceramics and diagnostic agents. The quantities to be used are the quantities customary for the use concerned.